The epidemiology of L carinii infection is poorly understood. Studies based on the presence of antibodies in serum suggest that most adults have been exposed to and been infected with P. carinii pneumonia. Thus the current concept for P. carinii pneumonia is that individuals are infected when they are young and are either asymptomatic or develop inapparent disease. Following such infection the organism becomes latent and can be reactivated at a time when the individual becomes immunosuppressed. Based on this hypothesis, one should be able to detect P. carinii in the lung tissue of a large number of individuals without P. carinii pneumonia. To investigate this hypothesis we are undertaking to evaluate pulmonary specimens from a variety of sources utilizing the PCR technique. This is a technique that allows amplification of very small amounts of DNA if the sequence for such DNA is known and primers for the PCR process can be synthesized. Recently the coding sequences for ribosomal RNA of P. carinii as well as for two enzymes, dihydrofolate reductase and thymidylate synthase, have become available. Ribosomal RNA sequences are being evaluated primarily since multiple gene copies are present in each genome. Primers specific for &carinii have been constructed and are currently in the process of being evaluated. Once the optimal conditions for these primers have been determined, the plan is to evaluate a large number of pulmonary specimens including bronchoalveolar lavage specimens from people with and without P. carinii pneumonia, as well as autopsy lung specimens, to look for the presence of P. carinii DNA. If such DNA can be found it suggests that in fact P. carnii organisms are present in a latent state. The technique will also be evaluated for ability to diagnose &carinii infection by examining sputum, blood, and other specimens. The goal of this phase of the study is to develop more sensitive non-invasive techniques for diagnosing this infection.